The ESR1 circulating mutations are commonly detectable 3 to 6 months before progression and are an important variability after end of AI exposure, Florian Clatot, MD, PhD, Centre Henri Becquerel, University of Normandy, Rouen, France, and colleagues reported.

Recently, the investigators found that detection of such mutations is related to AI resistance. For this study, they evaluated the predictive and prognostic values of circulating ESR1 mutations detected at disease progression.

The retrospective analysis included all consecutive patients treated from January 2008 through December 2010. Using plasma samples, rates of ESR1 circulating mutations — D538G, Y537S/N/C — were assessed using droplet digital PCR. Univariate and multivariate analyses were used to assess the effect of mutational status on overall survival, progression-free survival, and clinical response to subsequent treatments.

“At progression, 44 patients (30.6%) presented at least one ESR1 circulating mutation,” Dr. Clatot said. Of the total of 63 mutations, 19% of patients had a single mutation; 9%, a double mutation; and 2%, a triple mutation. The mutation type was D538G in 38%, Y537S in 33%, Y537N in 25%, and Y537C in 3%).

At a follow-up of 40 months (range, 4 to 94 months), there were 108 deaths. Median overall survival after progression was 15 months (range, 2 to 44 months) for patients with the mutations compared with 24 months (range, 2 to 70 months) for patients without mutations (hazard ratio [HR], 1.9; P = .006).

Treatment after progression on AI included 1 patient who was switched to another AI, 3 who had everolimus added, 19 who received chemotherapy, and 16 who received tamoxifen/fulvestrant. Five received “other/no treatment” and none received the addition of an HER2-inhibitor.